• Toxicological Research
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• 제24권2호
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• pp.101-107
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• 2008

Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

• 턱관절균형의학회지
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• 제9권1호
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• pp.4-11
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• 2019

Objectives: Although intraoral balancing appliance therapy has been used effective to several diseases, verification studies through cerebral diseases are poorly reported so far. Thus we investigated the effect of tooth-cut induced dental malocclusion against mouse model of ischemic stroke. Methods: Tooth-cut and 90 min middle cerebral artery occlusion (MCAO) were loaded to C57BL/6 male mice, and total infarct area, neurological deficit scores (NDS), histological change of hippocampal region were observed. Production levels of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in cerebral tissue were also measured. Results: The longer the tooth-cut period, the greater the area of cerebral infarction caused by MCAO, and NDS began to increase as the tooth was cut, and the results were more negative when MCAO was loaded. Histological change of hippocampal cells was significant when tooth-cut was maintained for 7 days. Those damages were thought to depend on the generation of ROS and iNOS in brain tissue. Conclusions: Since tooth-cut increased total area of cerebral infarction due to MCAO in mice, it is able to be confirmed that anomaly of the temporomandibular occlusion can affect neurological diseases.

• 대한한방내과학회지
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• 제27권1호
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• pp.265-275
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• 2006

Objectives : Electrical acupoint stimulation(EAS) has been used to treat motor dysfunction of stroke patients with reportedly effective results. The purpose of this study is to evaluate the efficacy of the EAS with different frequencies in treating motor dysfunction of ischemic stroke patients. Methods : The subject of this study were forty-two ischemic stroke patients with motor dysfunction in Kyunghee oriental medicine hospital who were hospitalized for one week to one month from onset. They were treated with 2Hz or 120Hz EAS for two weeks, and motor evoked potentials(MEP) were measured before and after EAS treatment. To compare the effect of 2Hz EAS with 120Hz, the number of patients who showed MEP responses after two weeks among those who had no previous response was checked. Also measured were latency, central motor conduction time(CMCT), amplitude of MEP before and after EAS treatment. Results : After two weeks of treatment, 4 out of 15 patients(27%) in the 2Hz EAS group and lout of 19 patients(5%) in the 120Hz group showed potential responses. Yet there was no significant difference between the two groups. When MEP data of the affected side between the 2Hz group and the 120Hz group was compared, the former showed more significant improvement than the latter in latency, CMCT and amplitude(P=0.040, 0.019,0.021). When the proportion of the affected side and unaffected side in MEP data was examined, the 2Hz group showed improvement on only latency and CMCT with significant differences(P=0.040, 0.014). Conclusions : These results show that EAS with low frequency is more helpful for motor recovery after ischemic stroke than that with high frequency. This suggests that low frequency EAS activates the central motor conduction system better than high frequency EAS.

• Journal of Preventive Medicine and Public Health
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• 제45권5호
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• pp.323-328
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• 2012

Objectives: Economic growth and development of medical technology help to improve the average life expectancy, but the western diet and rapid conversions to poor lifestyles lead an increasing risk of major chronic diseases. Coronary heart disease mortality in Korea has been on the increase, while showing a steady decline in the other industrialized countries. An age-period-cohort analysis can help understand the trends in mortality and predict the near future. Methods: We analyzed the time trends of ischemic heart disease mortality, which is on the increase, from 1985 to 2009 using an age-period-cohort model to characterize the effects of ischemic heart disease on changes in the mortality rate over time. Results: All three effects on total ischemic heart disease mortality were statistically significant. Regarding the period effect, the mortality rate was decreased slightly in 2000 to 2004, after it had continuously increased since the late 1980s that trend was similar in both sexes. The expected age effect was noticeable, starting from the mid-60's. In addition, the age effect in women was more remarkable than that in men. Women born from the early 1900s to 1925 observed an increase in ischemic heart mortality. That cohort effect showed significance only in women. Conclusions: The future cohort effect might have a lasting impact on the risk of ischemic heart disease in women with the increasing elderly population, and a national prevention policy is need to establish management of high risk by considering the age-period-cohort effect.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.531-538
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• 2015

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

• 대한한의학회지
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• 제28권1호통권69호
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• pp.35-41
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• 2007

Objectives : To gain better insights on the characteristics of stroke patients admitted to oriental medical hospitals, we analyzed the data of 363 consecutive patients with acute ischemic stroke from Hanbang Stroke Registry supported by the Ministry of Science and Technology of Korea. Methods : Subjects' enrollment was in the oriental medical hospitals of 3 universities located in the metropolitan region from October 2005 to October 2006. We assessed the subjects' general characteristics, risk factors, and etiology of stroke. Each patient's TOAST classification type was confirmed by two independent specialists. Those were small vessel occlusion (SVO), large artery atherosclerosis (LAA), cardioembolism (CE), stroke with other determined etiology (SOE), and stroke with undetermined etiology (SUE).Results 'The distribution of the subjects' general characteristics and risk factors for stroke were similar with result storm previous reports. However, in the TOAST classification, SVO was the major type occupying 78.5% in the total subjects, which is the highest share compared with other research with similar methods. These results imply that patients with more severe symptoms rarely visit oriental medical hospitals. Conclusion : Assuming that this research will continue adding patient's data continuously, this work will help us to understand the features of stroke patients at oriental medical hospitals, and contribute to expansion of the Korean Hanbang Stroke Data Bank.

• 대한한의학방제학회지
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• 제31권3호
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• pp.171-182
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• 2023

Objectives : Saposhnikoviae Radix (SR) and Glehniae Radix (GR) have been frequently used in traditional medicine to treat diseases related to 'wind' syndrome, but there have been cases where it has been mixed in a state where the plant of origin is not clear. In this study, to select materials for conducting preclinical cerebral infarction research, the network pharmacology analysis method was used to select suitable medicinal materials for the study. Methods : In this study, a Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) based network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3 were applied, then networks of bioactive compounds, target proteins, and target diseases was constructed. STRING database was used to construct a protein-protein interaction network. Results : It was confirmed that SR rather than GR has various target proteins and target diseases based on network pharmacological analysis using TCMSP database. And it was analyzed that the bioactive compounds only in SR act more on neurovascular diseases, and both drugs are expected to be effectively used for cardiovascular diseases. Conclusions : In our future study, SR will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• 대한중풍순환신경학회지
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• 제7권1호
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• pp.59-64
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• 2006

Objective : This study was aimed to investigated the warning signs and its relationship with the other characteristics in acute stroke patients. Methods : Three-hundred sixty three acute stroke patients were recuited in the oriental medical hospitals of 3 universities located in metropolitan region from October in 2005 to October in 2006. We evaluated their stroke type with brain MRI, their waring signs, and general characteristics such as age, sex, past history, risk factor, etc. Result : Of the 363 patient, 138(38%) patients were experience of warning signs. The frequency of Stress were found more in experience of warning signs than none of them. Warning signs were more common in Large Artery Atherosclerosis than in the other etiology. Conclusion : Although a concrete conclusion can hardly be drawn from this study, it reminds physicians of the importance of warning signs which their patients appeal. For the further investigation, it seems to be necessary to construct fundamental databases for stroke by increasing the number of patients and by examination into the etiology and location.

• 대한한방내과학회지
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• 제27권1호
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• pp.197-207
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• 2006

The object of this study was to examine the relationship between arteriosclerosis and oriental medical diagnosis of the patients who had suffered ischemic stroke. The degree of arteriosclerosis of the patients was assessed by cardio-ankle vascular index(CAVI), and diagnostic criteria used for all patients were deficiency of ki, deficiency of blood, blood stasis and stagnation of water. One hundred four patients were included and their general characteristics, CAVI and oriental diagnosis were evaluated. Results showed a significantly strong correlation between CAVI and blood stasis. These results suggest a close relationship between arterioslcerosis and blood static syndrome as defined by oriental medicine. If so, diagnosis of blood static syndrome is a reilable predictor of arteriosclerosis.

• 대한한의학회지
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• 제27권3호
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• pp.241-250
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• 2006

Backgrounds: Blood stasis is hon as an important pathologic factor for vascular disorder in Oriental medicine. Despite its clinical importance there have been few objective tests for diagnosing blood stasis. Objectives: This study was designed to examine the relationship between blood stasis and arterial stiffness measured by cardio-ankle vascular index (CAVI). Methods: The subjects were 104 ischemic stroke patients with onset after 14 days. Their general characteristics, lipid profiles and uric acid were recorded. The degree of arterial stiffness was assessed by CAVI, and blood stasis was evaluated by diagnostic criteria. The data were analyze4 by chi-square test, student t-test, spearman correlation analysis, and pearson correlation analysis. Then, stepwise multiple logistic regression analysis was applied in order to exclude the interactions among several factors. Results: There were significant differences in right, left and higher CAVI between the blood stasis group and the non blood stasis group (p-value<0.01). Age, systolic blood pressure, triglyceride and CAVI had relationships with blood static scores. In multiple logistic regression analysis, the adjusted odds ratio of blood stasis for arterial stiffness with CAVI above 9 were 7.091 (95% confidence interval, $1.641\sim30.638$). Conclusions: The results demonstrated the relationship between blood stasis and arterial stiffness measured by CAVI. Therefore, we suggest that CAVI should be one of the objective tests for diagnosing blood stasis.